A variety of applications exist in which the need to meter two or more liquids in accurately controlled proportions is critical. One such application is liquid chromatography wherein an analyte sample is passed in a flow of liquid solvent (the mobile phase) through a column packed with particulate matter (the stationary phase). While passing through the column, the various components in the sample separate from one another by adsorbing and desorbing from the stationary phase at different rates such that the individual components elute from the column at different times. The separated components flow through a detector which responds to each component and provides information to the user about the constituents of the sample.
To achieve more effective separations, high performance liquid chromatography (HPLC) systems often use mixtures of solvents as the mobile phase. When this mixture is held constant, the system operates in an isocratic mode. More conventionally, the system operates in a gradient mode whereby the components of the mixture are changed over time.
As used herein, a packet means a sequential contribution of fluid components provided to the pump intake. FIG. 1 graphically depicts an example of two consecutive packets where each packet includes contributions from a first solvent A, then a second solvent B, then a third solvent C and finally a fourth solvent D. A slice as used herein means the contribution of a single component to a packet. Thus the volume of component A in each packet is the first slice for the packet, the volume of component B in each packet represents the second slice for the packet, and so forth.
During gradient chromatography, metering and accuracy of the pump system is dependent on the valves controlling the volume of fluid drawn into the pump for each slice. Conventional metering techniques are based on an intake flow that accurately follows the commanded flow; however, the intake flow typically behaves like an underdamped system. FIG. 2 shows an example of the flow error due to the switching of a valve. As illustrated, the flow error is a decaying sinusoid. The flow errors for a given system vary according to the gas solubility, viscosity, and compliance of the solvents and other factors relating to hydraulic inertia. Subsequent switching of the valves typically results in errors in the relative proportions of the components unless the switching occurs at a zero error crossing. Moreover, each additional switching event similarly results in a new intake flow disturbance and corresponding flow error that can adversely affect the desired proportions of components.
Thus liquid chromatography performance being greatly dependent on the compositional accuracy of the solvent mixture is typically limited by errors due to the system intake response of the pump system and proportioning valve. The present invention addresses the need to reduce these errors.